European Radiology

, Volume 28, Issue 7, pp 3059–3065 | Cite as

Could IVIM and ADC help in predicting the KRAS status in patients with rectal cancer?

  • Yanyan Xu
  • Qiaoyu Xu
  • Hongliang Sun
  • Tongxi Liu
  • Kaining Shi
  • Wu Wang



To evaluate the diagnostic potential of DW-MRI relative parameters for differentiation of rectal cancers with different Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation status.


Fifty-one patients with rectal cancer underwent diffusion-weighted MR imaging with eight b values. ADCs (including Max-ADC, Min-ADC and Mean-ADC) and IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were respectively calculated by mono- and bi-exponential analysis. Patients were stratified into two groups: KRAS wild type and mutant. The DW-MRI-derived parameters between the KRAS wild-type group and KRAS mutant group were compared using the Mann-Whitney U test. Receiver-operating characteristic (ROC) analysis of discrimination between KRAS wild-type and KRAS mutant rectal cancer was performed for the DW-MRI-derived parameters.


Max-ADC, Mean-ADC and D values were significantly lower in the KRAS mutant group than in the KRAS wild-type group, whereas a higher D* value was demonstrated in the KRAS mutant group. According to the ROC curve, Mean-ADC and D* values showed moderate diagnostic significance with the AUC values of 0.756 and 0.710, respectively. The cut-off values for Mean-ADC and D* were 1.43 × 10-3mm2/s and 26.58 × 10-3mm2/s, respectively.


Rectal cancers had distinctive diffusion/perfusion characteristics in different KRAS mutation statuses. The DW-MRI-derived parameters, specifically Mean-ADC and D*, show a moderate diagnostic significance for KRAS status.

Key Points

• Rectal cancers with different KRAS mutation statuses demonstrated distinctive diffusion/perfusion characteristics.

• Max-ADC, Mean-ADC and D values were lower in the KRAS mutant group.

• A higher D* value was demonstrated in the KRAS mutant group.

• IVIM-DW MRI may potentially help preoperative KRAS mutant status prediction.


Rectal cancer Magnetic resonance imaging Diffusion Perfusion Mutation 



Apparent diffusion coefficient


Colorectal cancer


Diffusion coefficient


Pseudo-diffusion coefficient


Diffusion-weighted imaging


Epidermal growth factor receptor


Perfusion fraction


Intravoxel incoherent motion


Kirsten rat sarcoma viral oncogene homologue


Magnetic resonance imaging


National Comprehensive Cancer Network


Region of interest


Receiver-operating characteristic


Echo time


Repetition time


Turbo spin echo



This work was supported by grants from the National Natural Science Foundation of China (no. 81501469) and the Health Industry Special Scientific Research Project of the National Health and Family Planning Commission of the People’s Republic of China (no. 201402019).

Compliance with ethical standards


The scientific guarantor of this publication is Dr. Hongliang Sun.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived in this study.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• observational

• performed at one institution


  1. 1.
    Weizt J, Koch M, Debus J, Höhler T, Galle PR, Büchler MW (2005) Colorectal cancer. Lancet 365:153–165CrossRefGoogle Scholar
  2. 2.
    Migliore L, Migheli F, Spisni R, Coppedè F (2011) Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol. 2011:792362CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Brand TM, Wheeler DL (2012) KRAS mutant colorectal tumors: past and present. Small GTPases 3:34–39CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wang HL, Lopategui J, Amin MB, Patterson SD (2010) KRAS mutation testing in human cancers: The pathologist's role in the era of personalized medicine. Adv Anat Pathol 17:23–32PubMedGoogle Scholar
  5. 5.
    NCCN Clinical Practice Guidelines in Oncology: Colon Cancer (2016)-NCCN Evidence Blocks. National Comprehensive Cancer Network Web site. Published February 8, 2016.
  6. 6.
    NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer (2016)\ National Comprehensive Cancer Network Web site. Published November 4, 2015.
  7. 7.
    Bae H, Yoshida S, Matsuoka Y et al (2014) Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer. Int Urol Nephrol 46:555–561CrossRefPubMedGoogle Scholar
  8. 8.
    Higano S, Yun X, Kumabe T et al (2006) Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis. Radiology 241:839–846CrossRefPubMedGoogle Scholar
  9. 9.
    Curvo-Semedo L, Lambregts DM, Maas M, Beets GL, Caseiro-Alves F, Beets-Tan RG (2012) Diffusion-weighted MRI in rectal cancer: apparent diffusion coefficient as a potential noninvasive marker of tumor aggressiveness. J Magn Reson Imaging 35:1365–1371CrossRefPubMedGoogle Scholar
  10. 10.
    Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168:497–505CrossRefPubMedGoogle Scholar
  11. 11.
    Sun H, Xu Y, Xu Q et al (2017) Rectal cancer: Short-term reproducibility of intravoxel incoherent motion parameters in 3.0T magnetic resonance imaging. Medicine (Baltimore) 96:e6866CrossRefGoogle Scholar
  12. 12.
    Nougaret S, Vargas HA, Lakhman Y et al (2016) Intravoxel incoherent motion-derived histogram metrics for assessment of response after combined chemotherapy and radiation therapy in rectal cancer: initial experience and comparison between single-section and volumetric analyses. Radiology 280:446–454CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Xiao-ping Y, Jing H, Fei-ping L et al (2016) Intravoxel incoherent motion MRI for predicting early response to induction chemotherapy and chemoradiotherapy in patients with nasopharyngeal carcinoma. J Magn Reson Imaging 43:1179–1190CrossRefPubMedGoogle Scholar
  14. 14.
    Jenkinson MD, du Plessis DG, Smith TS, Brodbelt AR, Joyce KA, Walker C (2010) Cellularity and apparent diffusion coefficient in oligodendroglial tumours characterized by genotype. J Neuro oncol 96:385–392CrossRefGoogle Scholar
  15. 15.
    Guiu B, Petit JM, Capitan V et al (2012) Intravoxel incoherent motion diffusion-weighted imaging in nonalcoholic fatty liver disease: a 3.0-T MR study. Radiology 265:96–103CrossRefPubMedGoogle Scholar
  16. 16.
    Sun Y, Tong T, Cai S, Bi R, Xin C, Gu Y (2014) Apparent Diffusion Coefficient (ADC) Value: a potential imaging biomarker that reflects the biological features of rectal cancer. Plos One 9:e109371CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lai V, Li X, Lee VH et al (2014) Nasopharyngeal carcinoma: comparison of diffusion and perfusion characteristics between different tumour stages using intravoxel incoherent motion MR imaging. Eur Radiol 24:176–183CrossRefPubMedGoogle Scholar
  18. 18.
    Jung SH, Heo SH, Kim JW et al (2012) Predicting response to neoadjuvant chemoradiation therapy in locally advanced rectal cancer: diffusion-weighted 3 Tesla MR imaging. J Magn Reson Imaging 35:110–116CrossRefPubMedGoogle Scholar
  19. 19.
    Ward RL, Todd AV, Santiago F, O'Connor T, Hawkins NJ (1997) Activation of the K-ras oncogene in colorectal neoplasms is associated with decreased apoptosis. Cancer 79:1106–1113CrossRefPubMedGoogle Scholar
  20. 20.
    Kobayashi M, Watanabe H, Ajioka Y, Honma T, Asakura H (1996) Effect of K-ras mutation on morphogenesis of colorectal adenomas and early cancers: relationship to distribution of proliferating cells. Hum Pathol 27:1042–1049CrossRefPubMedGoogle Scholar
  21. 21.
    Shigenori K, Miho K, Shuhei T et al (2015) Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer. World J Gastroenterol 21:1275–1283CrossRefGoogle Scholar
  22. 22.
    Andreyev HJ, Norman AR, Cunningham D et al (2001) Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer 85:692–696CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Roth AD, Tejpar S, Delorenzi M et al (2010) Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 28:466–474CrossRefPubMedGoogle Scholar
  24. 24.
    Downward J (2003) Targeting RAS signaling pathways in the cancer therapy. Nat Rev Cancer 3:11–322CrossRefPubMedGoogle Scholar
  25. 25.
    Bazan V, Agnese V, Corsale S et al (2005) Specific TP53 and/ or K-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of 5-year Gruppo Oncologico dell’Italia Meridionale (GOIM) prospective study. Ann Oncol 16:iv50–iv55CrossRefPubMedGoogle Scholar
  26. 26.
    Li W, Qiu T, Zhi W et al (2015) Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages. BMC Cancer 15:340CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
  28. 28.
    Coppedè F, Lopomo A, Spisni R, Migliore L (2014) Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol 20:943–956CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Xu Q, Xu AT, Zhu MM, Tong JL, Xu XT, Ran ZH (2013) Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a meta-analysis. J Dig Dis 14:409–416CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Yanyan Xu
    • 1
  • Qiaoyu Xu
    • 1
  • Hongliang Sun
    • 1
  • Tongxi Liu
    • 1
  • Kaining Shi
    • 2
  • Wu Wang
    • 1
  1. 1.Department of RadiologyChina-Japan Friendship HospitalBeijingChina
  2. 2.Philips HealthcareBeijingChina

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